Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1\ua0year in patients aged >74\ua0years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5\ua0mg daily) with clopidogrel (75\ua0mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3\ua0days), subacute (4-30\ua0days), and late (31-365\ua0days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( Padj<0.001) without a difference in ADBRs ( Padj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( Padj<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( Padj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503

Concomitant use of proton pump inhibitors and dual antiplatelet therapy for cardiovascular outcomes

INTRODUCTION: The aim of this review is to discuss the consequences of potential pharmacokinetic interactions between proton pump inhibitors (PPIs) and antiplatelet therapy on cardiovascular (CV) outcomes and provide guidance on the management of concomitant use of PPIs in patients on dual antiplatelet therapy (DAPT). EVIDENCE ACQUISITION: DAPT combining aspirin and oral P2Y12 receptor inhibitors increases the risk of gastrointestinal (GI) bleeding, with higher rates of morbidity and mortality in patients undergoing percutaneous coronary intervention (PCI). PPIs are recommended in patients at risk of bleeding to reduce the risk of GI hemorrhage. PPIs can reduce the metabolism of Clopidogrel by competing with CYP450 enzymes, mostly CYP2C19 isoform. The clinical significance of this pharmacological interaction is not uniform in observational studies. The only randomized clinical trial assessing the clinical relevance of clopidogrel-omeprazole interaction showed that the use of omeprazole was associated with a reduction in GI bleeding, without any differences in CV outcomes. EVIDENCE SYNTHESIS: Several systematic reviews and meta-analyses suggest an increased risk of major adverse cardiovascular events (MACE), but not of mortality in patients with concomitant use of PPIs and Clopidogrel. Two metaanalysis studying the interactions between individual PPIs and Clopidogrel failed to demonstrate any strong relationships with adverse CV outcomes. CONCLUSIONS: PPIs should be administered in patients on DAPT at risk for GI bleeding. However the uncertain benefit of PPIs in patients who are not at risk of GI bleeding and the unclear risk in MACE suggest that caution should be used when prescribing PPIs in these patients

De-escalating dual antiplatelet therapy in patients with acute coronary syndromes : the right strategy to harmonize time-dependent ischemic and bleeding risk in elderly patients?

The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge

LINEE GUIDA PER LA TERAPIA ORTOPEDICA ED ORTODONTICA

Questo testo illustra in maniera dettagliata le Linee Guida per una terapia ortopedia delle malocclusioni scheletriche; sono inoltre descritte le modalità di trattamento mediante trattamento ortodontico fisso da eseguirsi preferibilmente dopo la terapia ortopedica

Linee guida per la terapia ortopedica ed ortodontica

Questo testo illustra in maniera dettagliata le Linee Guida per una terapia ortopedia delle malocclusioni scheletriche; sono inoltre descritte le modalità di trattamento mediante trattamento ortodontico fisso da eseguirsi preferibilmente dopo la terapia ortopedica

P997First experience in 19 months attain stability lv-lead extraction

Background: Two main issues in CRT are:1) obtain constant LV capture without PNS or lead dislodgment and 2) managing CIED infections. Active fixation LV lead Medtronic 20066 Attain Stability allows lead fixation in the target CS vein but there are no long term extraction success data. We report our experience in extraction of this lead, 19 months after implantation. Clinical Case: 84 y.o. man affected by chronic ischemic cardiopaty with severe left ventricular dysfunction (LVEF 25%) and left bundle branch block (native QRS: 180 msec). Implanted with CRT-D (2012) and undergone to malfunctioning LV-lead extraction and reimplantation with a Medtronic 20066 Attain Stability active fixation LV lead (February 2015), he was admitted in our facility in September 2016 diagnosed with pocket infection after complete laboratory and imaging assessment. Patient underwent to CRT-D explant and lead extraction procedure. We performed manual technique using 10-11F mechanical dilator sheats for passive fixation atrial lead and ventricular dual coil active fixation lead. LV lead was armed with non-autolocking stylet, disanchored with just 4 counterclockwise rotations and simply retrieved with manual traction. Procedure was well tolerated without any complication. After 21 days of targeted anthibiotic therapy, patient was right-sided reimplanted with CRT-D and a new Attain Stability Lead in the same PL branch of CS of former one. Conclusions: in our experience, Medtronic Attain Stability active fixation LV lead showed to be safely and effectively extracted, aven 19 months after implantation, as never reported before in literature